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Translational Research: the Journal of Laboratory and Clinical Medicine

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https://www.readbyqxmd.com/read/30423312/glycomics-in-rare-diseases-from-diagnosis-to-mechanism
#1
Mariska Davids, Megan S Kane, Lynne A Wolfe, Camilo Toro, Cynthia J Tifft, David Adams, Xueli Li, Mohd A Raihan, Miao He, William A Gahl, Cornelius F Boerkoel, May Christine V Malicdan
The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) studies rare genetic disorders not only to achieve diagnoses, but to understand human biology. To ascertain the contribution of protein glycosylation to rare diseases, the NIH UDP used mass spectrometry to agnostically identify abnormalities of N-linked and O-linked glycans in plasma and free oligosaccharides in the urine of 207 patients. 60% of UDP patients had a glycome profile that deviated from control values in at least 1 fluid...
October 23, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30399369/a-small-molecule-hedgehog-agonist-hhag1-5-mediated-reprogramming-breaks-the-quiescence-of-noninjured-liver-stem-cells-for-rescuing-liver-failure
#2
Abhisek Mitra, Jun Yan, Liangfang Zhang, Shulin Li
Liver is the second most transplanted organ according to United network for organ sharing. Due to shortage of compatible donors, surgical difficulties, immunological hindrance, and high postoperative cost, stem cell therapy is an attractive substitute of liver transplant for millions of patients suffering from hepatic failure. Due to several technical limitations such as viral integration, inefficient differentiation, and adult phenotypes and epigenetic memory of fibroblasts, induced pluripotent stem cells, mesenchymal stem cells, or induced hepatocyte may not present a great clinical substitute for liver transplant...
October 19, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30391475/epigenetics-in-amyotrophic-lateral-sclerosis-a-role-for-histone-post-translational-modifications-in-neurodegenerative-disease
#3
REVIEW
Seth A Bennett, Royena Tanaz, Samantha N Cobos, Mariana P Torrente
Amyotrophic lateral sclerosis (ALS) is the third most common adult onset neurodegenerative disorder worldwide. It is generally characterized by progressive paralysis starting at the limbs ultimately leading to death caused by respiratory failure. There is no cure and current treatments fail to slow the progression of the disease. As such, new treatment options are desperately needed. Epigenetic targets are an attractive possibility because they are reversible. Epigenetics refers to heritable changes in gene expression unrelated to changes in DNA sequence...
October 12, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30391474/liquid-biopsy-in-ovarian-cancer-the-potential-of-circulating-mirnas-and-exosomes
#4
REVIEW
Lydia Giannopoulou, Martha Zavridou, Sabine Kasimir-Bauer, Evi S Lianidou
Ovarian cancer still remains the most lethal female cancer, since in most cases it is diagnosed at an advanced stage. Usually after completion of primary treatment chemoresistance occurs, and recurrent disease is finally observed. Liquid biopsy, based on minimally invasive and serial blood tests, has the advantage of following tumor evolution in real time, offering novel insights on precision medicine. Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating cell-free microRNAs (cfmiRNAs) and circulating exosomes represent the major components of liquid biopsy analysis...
October 12, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30392877/targeting-epigenetic-mechanisms-in-diabetic-wound-healing
#5
REVIEW
Aaron Den Dekker, Frank M Davis, Steve L Kunkel, Katherine A Gallagher
Impaired wound healing is a major secondary complication of type 2 diabetes that often results in limb loss and disability. Normal tissue repair progresses through discrete phases including hemostasis, inflammation, proliferation, and remodeling. In diabetes, normal progression through these phases is impaired resulting in a sustained inflammatory state and dysfunctional epithelialization in the wound. Due to their plasticity, macrophages play a critical role in the transition from the inflammation phase to the proliferation phase...
October 10, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30392876/circulating-mir-143-3p-inhibition-protects-against-insulin-resistance-in-metabolic-syndrome-via-targeting-of-the-insulin-like-growth-factor-2-receptor
#6
Lin Xihua, Tang Shengjie, Gui Weiwei, Erik Matro, Tao Tingting, Li Lin, Wu Fang, Zhou Jiaqiang, Zheng Fenping, Li Hong
Metabolic syndrome (MetS) is characterized by a cluster of metabolic disorders including obesity, dyslipidemia, hyperglycemia, and hypertension. Here, we report that 27 microRNAs were found to be expressed differently in serum and urine samples of MetS patients compared to control subjects on microarray analysis. Further qualitative real time- polymerase chain reaction analyses confirmed that circulating levels of miR-143-3p were significantly elevated in MetS patients compared with controls, both in serum and urine samples...
October 9, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30347179/a-long-term-treatment-with-taurine-prevents-cardiac-dysfunction-in-mdx-mice
#7
Antonietta Mele, Paola Mantuano, Michela De Bellis, Francesco Rana, Francesca Sanarica, Elena Conte, Maria Grazia Morgese, Maria Bove, Jean-Francois Rolland, Roberta Francesca Capogrosso, Sabata Pierno, Giulia Maria Camerino, Luigia Trabace, Annamaria De Luca
Taurine is an amino acid abundantly present in heart and skeletal muscle. Duchenne muscular dystrophy (DMD) is a genetic disorder in which the absence of dystrophin leads to skeletal muscle wasting and heart failure. An altered taurine metabolism has been described in dystrophic animals and short-term taurine administration exerts promising amelioration of early muscular alterations in the mdx mouse model of DMD. To reinforce the therapeutic and nutraceutical taurine potential in DMD, we evaluated the effects of a long-term treatment on cardiac and skeletal muscle function of mdx mice in a later disease stage...
September 28, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30342797/proteasome-biology-and-therapeutics-in-cardiac-diseases
#8
REVIEW
Sanket Kumar Shukla, Khadija Rafiq
The ubiquitin proteasome system (UPS) is the major pathway for intracellular protein degradation in most organs, including the heart. UPS controls many fundamental biological processes such as cell cycle, cell division, immune responses, antigen presentation, apoptosis, and cell signaling. The UPS not only degrades substrates but also regulates activity of gene transcription at the post-transcription level. Emerging evidence suggests that impairment of UPS function is sufficient to cause a number of cardiac diseases, including heart failure, cardiomyopathies, hypertrophy, atrophy, ischemia-reperfusion, and atherosclerosis...
September 28, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30342000/smad7-is-a-novel-independent-predictor-of-survival-in-patients-with-cutaneous-melanoma
#9
Maciej Kaczorowski, Przemyslaw Biecek, Piotr Donizy, Malgorzata Pieniazek, Rafal Matkowski, Agnieszka Halon
Overexpression of SMAD7-a hallmark inhibitor of transforming growth factor β (TGFβ) signaling-has been documented and related with adverse prognosis in a number of epithelial malignancies, suggesting that it may be responsible for resistance to TGFβ-induced growth arrest of cancer cells. The involvement of SMAD7 in development and progression of malignant melanoma is unclear, and its expression has not been characterized so far at the protein level in clinical melanoma tissue samples. We evaluated SMAD7 expression in 205 skin melanoma primary tumors by immunohistochemistry and correlated the findings with clinicopathological profiles of patients...
September 27, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30304666/epigenetic-alterations-caused-by-aflatoxin-b1-a-public-health-risk-in-the-induction-of-hepatocellular-carcinoma
#10
REVIEW
Roseane Guimarães Ferreira, Magda Vieira Cardoso, Karine Maria de Souza Furtado, Kaio Murilo Monteiro Espíndola, Ruanderson Pereira Amorim, Marta Chagas Monteiro
Aflatoxin B1 (AFB1) is currently the most commonly studied mycotoxin due to its great toxicity, its distribution in a wide variety of foods such as grains and cereals and its involvement in the development of + (hepatocellular carcinoma; HCC). HCC is one of the main types of liver cancer, and has become a serious public health problem, due to its high incidence mainly in Southeast Asia and Africa. Studies show that AFB1 acts in synergy with other risk factors such as hepatitis B and C virus leading to the development of HCC through genetic and epigenetic modifications...
September 15, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30287243/aldh1-positive-intratumoral-stromal-cells-indicate-differentiated-epithelial-like-phenotype-and-good-prognosis-in-prostate-cancer
#11
Paulina Nastały, Martyna Filipska, Colm Morrissey, Elke Eltze, Axel Semjonow, Burkhard Brandt, Klaus Pantel, Natalia Bednarz-Knoll
Aldehyde dehydrogenase 1 (ALDH1) characterizes tumor-initiating cells in solid tumors; however, little is known about its expression in intratumoral stromal cells. Herein, we aimed to dissect its potential dual relevance in prostate cancer (PCa). ALDH1 expression was evaluated immunohistochemically in tumor and stromal cells in primary PCa and metastases. It was correlated to clinico-pathologic parameters, patients' outcome, and selected proteins (CK5/6, CK14, CK8/18, CK19, EpCAM, Ki-67, E-cadherin, N-cadherin, and vimentin)...
September 12, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30213530/toward-genome-editing-in-x-linked-rp-development-of-a-mouse-model-with-specific-treatment-relevant-features
#12
J Schlegel, J Hoffmann, D Röll, B Müller, S Günther, W Zhang, A Janise, C Vössing, B Fühler, J Neidhardt, H Khanna, B Lorenz, K Stieger
Genome editing represents a powerful tool to treat inherited disorders. Highly specific endonucleases induce a DNA double strand break near the mutant site, which is subsequently repaired by cellular DNA repair mechanisms that involve the presence of a wild type template DNA. In vivo applications of this strategy are still rare, in part due to the absence of appropriate animal models carrying human disease mutations and knowledge of the efficient targeting of endonucleases. Here we report the generation and characterization of a new mouse model for X-linked retinitis pigmentosa (XLRP) carrying a point mutation in the mutational hotspot exon ORF15 of the RPGR gene as well as a recognition site for the homing endonuclease I-SceI...
August 24, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30401465/epigenetic-regulators-of-programmed-death-ligand-1-expression-in-human-cancers
#13
REVIEW
Sachin Kumar, Surender Kumar Sharawat
The programmed cell death protein 1-programmed death-ligand 1 (PD-L1) axis has been successfully targeted in clinics and the use of immune check-point inhibitors have shown durable antitumor response in untreated or heavily treated advanced stage cancer. PD-L1 upregulation has been found to correlate with poor prognosis in multiple cancer types and expression of PD-L1 in intratumoral compartment has been suggested to influence immune response and act as a key determinant of checkpoint immunotherapy efficacy...
December 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30165038/mitochondria-in-innate-immune-signaling
#14
REVIEW
Balaji Banoth, Suzanne L Cassel
Mitochondria are functionally versatile organelles. In addition to their conventional role of meeting the cell's energy requirements, mitochondria also actively regulate innate immune responses against infectious and sterile insults. Components of mitochondria, when released or exposed in response to dysfunction or damage, can be directly recognized by receptors of the innate immune system and trigger an immune response. In addition, despite initiation that may be independent from mitochondria, numerous innate immune responses are still subject to mitochondrial regulation as discrete steps of their signaling cascades occur on mitochondria or require mitochondrial components...
December 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30144425/mitochondrial-regulation-of-diabetic-vascular-disease-an-emerging-opportunity
#15
REVIEW
Michael E Widlansky, R Blake Hill
Diabetes-related vascular complication rates remain unacceptably high despite guideline-based medical therapies that are significantly more effective in individuals without diabetes. This critical gap represents an opportunity for researchers and clinicians to collaborate on targeting mechanisms and pathways that specifically contribute to vascular pathology in patients with diabetes mellitus. Dysfunctional mitochondria producing excessive mitochondrial reactive oxygen species (mtROS) play a proximal cell-signaling role in the development of vascular endothelial dysfunction in the setting of diabetes...
December 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30118659/functional-characterization-of-alternatively-spliced-gsn-in-head-and-neck-squamous-cell-carcinoma
#16
Dylan Z Kelley, Emily L Flam, Theresa Guo, Ludmila V Danilova, Fernando T Zamuner, Craig Bohrson, Michael Considine, Eric J Windsor, Justin A Bishop, Chi Zhang, Wayne M Koch, David Sidransky, William H Westra, Christine H Chung, Joseph A Califano, Sarah Wheelan, Alexander V Favorov, Liliana Florea, Elana J Fertig, Daria A Gaykalova
We have recently performed the characterization of alternative splicing events (ASEs) in head and neck squamous cell carcinoma, which allows dysregulation of protein expression common for cancer cells. Such analysis demonstrated a high ASE prevalence among tumor samples, including tumor-specific alternative splicing in the GSN gene.In vitro studies confirmed that overall expression of either ASE-GSN or wild-type GSN (WT-GSN) isoform inversely correlated with cell proliferation, whereas the high ratio of ASE-GSN to WT-GSN correlated with increased cellular invasion...
December 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30301522/novel-biomarkers-in-multiple-myeloma
#17
REVIEW
Adam Levin, Parameswaran Hari, Binod Dhakal
Significant advancements have been made in the molecular mechanisms of myelomagenesis, diagnostic methods, prognostication, and the treatment options in multiple myeloma (MM) over the last decade. Despite these, MM remains a heterogeneous disease with differing outcomes. As myeloma treatment landscape continues to expand, personalized treatment that provides maximum benefit to a specific patient becomes more important. In the last few years, serum monoclonal proteins including the serum-free light chain assays, imaging, and cytogenetics have been used to predict the outcomes of MM patients receiving different types of therapies...
November 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30144424/serum-biomarkers-for-diagnosis-and-prediction-of-type-1-diabetes
#18
REVIEW
Lian Yi, Adam C Swensen, Wei-Jun Qian
Type 1 diabetes (T1D) culminates in the autoimmune destruction of the pancreatic βcells, leading to insufficient production of insulin and development of hyperglycemia. Serum biomarkers including a combination of glucose, glycated molecules, C-peptide, and autoantibodies have been well established for the diagnosis of T1D. However, these molecules often mark a late stage of the disease when ∼90% of the pancreatic insulin-producing β-cells have already been lost. With the prevalence of T1D increasing worldwide and because of the physical and psychological burden induced by this disease, there is a great need for prognostic biomarkers to predict T1D development or progression...
November 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30075099/circulating-tumor-cells-as-liquid-biopsies-to-understand-cancer-metastasis
#19
REVIEW
Dennis Woo, Min Yu
Circulating tumor cells (CTCs) are a subset of cancer cells that are shed from the primary or metastatic tumors into the bloodstream. CTCs are responsible for the establishment of blood-borne distant metastases but their rarity, estimated at one CTC per billion blood cells, presents the biggest technical barrier to their functional studies. Recent advances in CTC isolation technology have allowed for the reliable capture of CTCs from the whole blood of cancer patients. The ability to derive clinically relevant information from CTCs isolated through a blood draw allows for the monitoring of active disease, avoiding the invasiveness inherent to traditional biopsy techniques...
November 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30031766/molecular-assessment-of-circulating-exosomes-toward-liquid-biopsy-diagnosis-of-ewing-sarcoma-family-of-tumors
#20
REVIEW
Peng Zhang, Glenson Samuel, Jennifer Crow, Andrew K Godwin, Yong Zeng
Ewing sarcoma was first described in 1921 in the Proceedings of the New York Pathological Society by an eminent American pathologist from Cornell named James R. Ewing as a "diffuse endothelioma of bone." Since this initial description, more has been discovered regarding Ewing sarcoma and in the 1980's both Ewing sarcoma and peripheral primitive neuroectodermal tumors due to their similar features and shared identical genetic abnormality were grouped into a class of cancers entitled Ewing sarcoma family of tumors (ESFTs)...
November 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
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